Folding Pathway of a Lattice Model for Proteins

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1999 Feb 17

PMID 9990014

Citations 21

Authors

V S Pande

D S Rokhsar

Affiliations

Soon will be listed here.

Abstract

The folding of a protein-like heteropolymer is studied by using direct simulation of a lattice model that folds rapidly to a well-defined "native" structure. The details of each molecular folding event depend on the random initial conformation as well as the random thermal fluctuations of the polymer. By analyzing the statistical properties of hundreds of folding events, a classical folding "pathway" for such a polymer is found that includes partially folded, on-pathway intermediates that are shown to be metastable equilibrium states of the polymer. These results are discussed in the context of the "classical" and "new" views of folding.

Citing Articles

High Energy Channeling and Malleable Transition States: Molecular Dynamics Simulations and Free Energy Landscapes for the Thermal Unfolding of Protein U1A and 13 Mutants.

Dang N, Baranger A, Beveridge D Biomolecules. 2022; 12(7).

PMID: 35883496 PMC: 9312810. DOI: 10.3390/biom12070940.

The Early Phase of β2-Microglobulin Aggregation: Perspectives From Molecular Simulations.

Loureiro R, Faisca P Front Mol Biosci. 2020; 7:578433.

PMID: 33134317 PMC: 7550760. DOI: 10.3389/fmolb.2020.578433.

Conformational Intermediate That Controls KPC-2 Catalysis and Beta-Lactam Drug Resistance.

Cortina G, Hays J, Kasson P ACS Catal. 2019; 8(4):2741-2747.

PMID: 30637173 PMC: 6324736. DOI: 10.1021/acscatal.7b03832.

On the characterization and software implementation of general protein lattice models.

Bechini A PLoS One. 2013; 8(3):e59504.

PMID: 23555684 PMC: 3612044. DOI: 10.1371/journal.pone.0059504.

Comparative modeling and protein-like features of hydrophobic-polar models on a two-dimensional lattice.

Moreno-Hernandez S, Levitt M Proteins. 2012; 80(6):1683-93.

PMID: 22411636 PMC: 3348970. DOI: 10.1002/prot.24067.

References

Taketomi H, Ueda Y, Go N . Studies on protein folding, unfolding and fluctuations by computer simulation. I. The effect of specific amino acid sequence represented by specific inter-unit interactions. Int J Pept Protein Res. 1975; 7(6):445-59. View

Dill K, Shortle D . Denatured states of proteins. Annu Rev Biochem. 1991; 60:795-825. DOI: 10.1146/annurev.bi.60.070191.004051. View

Kim P, Baldwin R . Intermediates in the folding reactions of small proteins. Annu Rev Biochem. 1990; 59:631-60. DOI: 10.1146/annurev.bi.59.070190.003215. View

PTITSYN O, Pain R, Semisotnov G, Zerovnik E, Razgulyaev O . Evidence for a molten globule state as a general intermediate in protein folding. FEBS Lett. 1990; 262(1):20-4. DOI: 10.1016/0014-5793(90)80143-7. View

Skolnick J, Kolinski A . Dynamic Monte Carlo simulations of globular protein folding/unfolding pathways. I. Six-member, Greek key beta-barrel proteins. J Mol Biol. 1990; 212(4):787-817. DOI: 10.1016/0022-2836(90)90237-g. View

Kuwajima K . The molten globule state as a clue for understanding the folding and cooperativity of globular-protein structure. Proteins. 1989; 6(2):87-103. DOI: 10.1002/prot.340060202. View

McCammon J, Karplus M . Dynamics of activated processes in globular proteins. Proc Natl Acad Sci U S A. 1979; 76(8):3585-9. PMC: 383876. DOI: 10.1073/pnas.76.8.3585. View

Fersht A . Optimization of rates of protein folding: the nucleation-condensation mechanism and its implications. Proc Natl Acad Sci U S A. 1995; 92(24):10869-73. PMC: 40532. DOI: 10.1073/pnas.92.24.10869. View

Abkevich V, Gutin A, Shakhnovich E . Domains in folding of model proteins. Protein Sci. 1995; 4(6):1167-77. PMC: 2143143. DOI: 10.1002/pro.5560040615. View

10.

Schindler T, Herrler M, Marahiel M, Schmid F . Extremely rapid protein folding in the absence of intermediates. Nat Struct Biol. 1995; 2(8):663-73. DOI: 10.1038/nsb0895-663. View

11.

Bai Y, Sosnick T, Mayne L, Englander S . Protein folding intermediates: native-state hydrogen exchange. Science. 1995; 269(5221):192-7. PMC: 3432310. DOI: 10.1126/science.7618079. View

12.

Huang G, Oas T . Submillisecond folding of monomeric lambda repressor. Proc Natl Acad Sci U S A. 1995; 92(15):6878-82. PMC: 41433. DOI: 10.1073/pnas.92.15.6878. View

13.

Sali A, Shakhnovich E, Karplus M . How does a protein fold?. Nature. 1994; 369(6477):248-51. DOI: 10.1038/369248a0. View

14.

PTITSYN O . Structures of folding intermediates. Curr Opin Struct Biol. 1995; 5(1):74-8. DOI: 10.1016/0959-440x(95)80011-o. View

15.

Fersht A . Characterizing transition states in protein folding: an essential step in the puzzle. Curr Opin Struct Biol. 1995; 5(1):79-84. DOI: 10.1016/0959-440x(95)80012-p. View

16.

Otzen D, Itzhaki L, elMasry N, Jackson S, Fersht A . Structure of the transition state for the folding/unfolding of the barley chymotrypsin inhibitor 2 and its implications for mechanisms of protein folding. Proc Natl Acad Sci U S A. 1994; 91(22):10422-5. PMC: 45032. DOI: 10.1073/pnas.91.22.10422. View

17.

Dobson C . Protein folding. Solid evidence for molten globules. Curr Biol. 1994; 4(7):636-40. DOI: 10.1016/s0960-9822(00)00141-x. View

18.

Abkevich V, Gutin A, Shakhnovich E . Specific nucleus as the transition state for protein folding: evidence from the lattice model. Biochemistry. 1994; 33(33):10026-36. DOI: 10.1021/bi00199a029. View

19.

Jennings P, Wright P . Formation of a molten globule intermediate early in the kinetic folding pathway of apomyoglobin. Science. 1993; 262(5135):892-6. DOI: 10.1126/science.8235610. View

20.

Matthews C . Pathways of protein folding. Annu Rev Biochem. 1993; 62:653-83. DOI: 10.1146/annurev.bi.62.070193.003253. View